PROJECT SUMMARY - STRUCTURAL BIOLOGY SHARED RESOURCE The Structural Biology Shared Resource (SBSR) provides comprehensive services and technologies for the generation of high resolution structural (X-ray, NMR, Cryo-EM) and proteomics analyses, and the technical expertise and intellectual infrastructure for interpretation and leveraging of these data to drive biochemical, cell biological and genetic experiments to discover novel biological processes and targets that lead to new therapeutic strategies. These traditional structural and proteomics methods are complemented by a wide range of computational, biochemical and biophysical approaches within Einstein and the AECC. The SBSR also provides considerable expertise in protein science, offering state-of-the-art automated capabilities in protein expression and purification, and receptor-ligand interaction analysis. Over the past funding period there have been significant technical, leadership, administrative and organizational enhancements. (i) The current AECC- supported Proteomics resource has been merged into the Structure Biology Shared Resource (SBSR) to capitalize on the scientific, technical and administrative synergies of this union, and an exceptional Proteomics co-director, Simone Sidoli from the U. of Penn, has been recruited. As part of this recruitment, the College has committed to the purchase of state-of-the-art instrumentation; (ii) A new senior co-director, David Cowburn, was recruited to lead the NMR component, providing enhanced capabilities in NMR and enhanced access to the New York Structural Biology Center with its expanded world-class cryo-electron microscopy infrastructure; (iii) There is now extensive access to the unique X-ray diffraction infrastructure at the newly established National Synchrotron Light Source-II (NSLS-II) at Brookhaven National Laboratory, as well as continued access to resources at Argonne National Laboratory; (iv) a new in-house X-ray data collection system was obtained through an NIH shared instrumentation grant; and v) with College support, high-throughput CRISPR screening and mAb discovery platforms have been implemented in association with the SBSR. Taken together, this unique set of technologies, and associated expert technical staff, supports a broad spectrum of studies on fundamental mechanisms underlying cancer biology, and enables the development of small molecules and biologics for novel treatment strategies that have resulted in considerable intellectual property and commercialization opportunities.